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ORIGINAL ARTICLE
Year : 2020  |  Volume : 8  |  Issue : 4  |  Page : 184-189

A study of the comparative clinical profiles of scrub typhus, spotted fever group, and typhus group rickettsial infections at a rural tertiary care hospital


Department of Medicine, MVJ MC and RH, Bengaluru, Karnataka, India

Date of Submission14-Dec-2019
Date of Decision18-Jan-2020
Date of Acceptance24-Apr-2020
Date of Web Publication23-Oct-2020

Correspondence Address:
Dr. Shreyashi Ganguly
Department of Medicine, MVJ MC and RH, Hoskote, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJIM.AJIM_86_19

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  Abstract 


Background: The rickettsioses represent a major cause of acute febrile illnesses worldwide. The greatest challenge lies in diagnosing rickettsioses in a timely manner early in the course, when antibiotic use is most effective. In most cases clinical suspicion together with a positive serology is employed to make the diagnosis of rickettsiosis. Aim and Objective: To study the syndromic differences, if any, amongst the three groups of rickettsial infections present in India. Methods: This was a cross-sectional observational study that evaluated a total of 172 cases of rickettsial fever out of a pool of 778 cases of acute febrile illness between the June 2017 and March 2019. A careful search for eschar, lymphadenopathy and rashes was made. Weil Felix test was done after exclusion of other infections like malaria, dengue, enteric fever. To avoid the possibility of false positives, a single titer dilution >1:320 was considered positive for rickettsioses. Results: Fever was seen in all cases. Myalgia (81·5%), headache (72·8%), and splenomegaly (51·9%) were common in scrub typhus. Eschar was seen in only 8·4% cases. Spotted fever group presented with fever of shorter duration of less than seven days (64·7%), and gastrointestinal symptoms like vomiting (74·5%) and diarrhea (13·7%) were predominantly seen. Spotted fever group had macular rash as predominant sign. Typhus group presented with fever of longer duration of more than fourteen days (50%) and respiratory symptoms like cough (65%). Hepatomegaly was present in 35% and lymphadenopathy in 7·5%. Conclusion: Rrickettsial infections remain a diagnostic challenge in resource-poor settings. Therefore, it is important to recognize the clinical features promptly, include rickettsioses in the differential diagnoses, and consider early initiation of appropriate treatment.

Keywords: Comparative clinical profile, doxycyclic, rickettsial infections, rickettsial syndromes, scrub typhus, spotted fever group


How to cite this article:
Kamath V, Bindu B H, Ganguly S. A study of the comparative clinical profiles of scrub typhus, spotted fever group, and typhus group rickettsial infections at a rural tertiary care hospital. APIK J Int Med 2020;8:184-9

How to cite this URL:
Kamath V, Bindu B H, Ganguly S. A study of the comparative clinical profiles of scrub typhus, spotted fever group, and typhus group rickettsial infections at a rural tertiary care hospital. APIK J Int Med [serial online] 2020 [cited 2020 Nov 30];8:184-9. Available from: https://www.ajim.in/text.asp?2020/8/4/184/298947




  Introduction Top


The rickettsioses represent a major cause of acute febrile illnesses worldwide. Rickettsial infections which were initially seen in epidemic forms had disappeared with the widespread use of insecticides to control vectors and use of tetracyclines as the first-line antibiotics by practitioners. However, the indiscriminate use of tetracyclines has declined due to the adoption of better antibiotic policies. In addition, the urbanization of rural areas has exposed more of the population to the potential sources of infection. These two factors have coincided with the re-emergence of this deadly scourge.[1]

In India, 11 outbreaks have been reported from 2000 to 2011, with >900 cases and 42 deaths (case-fatality rate: 5%–17%) in Himachal Pradesh, Manipur, and one each from Jammu and Kashmir, Tamil Nadu, Puducherry, West Bengal, and Meghalaya. Scrub typhus caused all the outbreaks (exception Kangra: Epidemic typhus).[1] Cases have also been reported from Rajasthan, Uttaranchal, Assam, Maharashtra, Kerala, and Karnataka.[1]

These diseases can be incapacitating and difficult to diagnose in resource-poor settings. Under-recognition and under-testing of potential cases, lack of facilities for testing, and nonstandardized reporting systems likely contribute to the increased burden of morbidity and mortality.[2]

Untreated cases have a fatality of up to 30%,[1],[3] but when promptly and properly diagnosed, it is often easily treated. Physicians caring for the local populace and febrile returned travelers face the extremely difficult task of recognizing and differentiating rickettsial infections from other equally prevalent and important diseases. The greatest challenge lies in diagnosing rickettsioses in a timely manner early in the course, when antibiotic use is most effective.

Rickettsioses have no pathognomonic signs, although there are signs and symptoms that are highly suggestive, such as the presence of fever, rash, lymphadenopathy, and an eschar (tachè noire). Unfortunately, not always and not all rickettsioses present typical signs and symptoms. In most cases, clinical suspicion together with a positive serology is employed to make the diagnosis of rickettsiosis.[4]

Weil-Felix test (WFT) is easily available for the diagnosis in India but must be interpreted in the correct clinical context. Sensitivity and specificity of WFT in relation to scrub typhus immunoglobulin M (IgM) ELISA at a titer of 160 were 72.5% and 91.4%, respectively. As the titers increased, the WFT is more specific.[5] In comparison to immunofluorescent antibody assay (IFA), WFT has a sensitivity of 33% and specificity of 46% for the spotted fever group (SFG).[6] Using immunoperoxidase assay for comparison, at ccc (sensitivity = 43.6% and specificity = 95.9%) reacted with antibodies against typhus group.[7] Other serological tests are based on detecting antibodies and aid in the diagnosis only 5–7 days after the onset of the disease. These are not helpful in the early initiation of therapy in a suspected case.[8] Immunofluorescence assay (IFA), the gold standard diagnostic test for rickettsial infections, is not easily available in India. It is expensive and can take more than a week to get the results.[9] As no single laboratory finding is specific for the early diagnosis, the treatment needs to be started on clinical suspicion. In this study, we present a comparative clinical and laboratory profile of 172 patients diagnosed with rickettsioses.


  Materials and Methods Top


This is a prospective, observational study conducted in the hospital between June 2017 and March 2019. A total of 778 cases of acute febrile illness were admitted to the hospital during this time. Detailed clinical examination of each patient was done including careful search for eschar, lymphadenopathy, and rashes. Basic hematological and biochemical tests were done in these cases (complete blood count, urine analysis, blood sugars, renal function, and liver function tests). WFT was done after the exclusion of other infections such as malaria, dengue, and enteric fever. To avoid the possibility of false positives, a single titer dilution >1:320 was considered positive. Other investigations such as chest X-ray, ultrasound abdomen, and cerebrospinal fluid analysis were done when indicated. A total of 172 (22.1%) patients were diagnosed to have rickettsial infection. The patients were again divided into scrub typhus group (Ox-K+), SFG (Ox-19 and Ox-2+), and typhus group (Ox-19+) depending on WFT results.[1],[8] All typical and atypical manifestations were noted. The outcome of the patients including complications in each group was evaluated. Once diagnosed, all patients were treated appropriately with doxycycline, and the response to the therapy was noted. Descriptive statistics and analytical statistics in the form of analysis of variance (ANOVA) were performed to compare the means between three or more distinct/independent groups with the data obtained. P < 0.05 was considered statistically significant.


  Results Top


A total of 778 cases of acute febrile illness were admitted to our hospital during the study period. One hundred and seventy-two (22·1%) patients were diagnosed with rickettsial fever. Of these patients, 81 patients were diagnosed to have scrub typhus, 51 patients belonged to the SFG, and 40 cases to the typhus group.

Seasonal variation was noted in the occurrence of scrub typhus. Most patients presented in the month of June–August [Figure 1]. Patients in spotted fever and typhus group infection showed no seasonal pattern.
Figure 1: Seasonal variation in rickettsial cases

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The age of the patients ranged from 18 to 65 years. Most of the patients were young, with a mean age group of 39·2 ± 8·4 years. There was a nonsignificant male preponderance (ratio male:female: 1.l:l, P = 0·78). Eighty-six percent of the patients belonged to the rural area and poor socioeconomic status.

Agriculture was the predominant occupation among those afflicted.

The most common presenting symptom was fever (n = 172, 100%) throughout the groups. Scrub typhus group patients presented with fever of duration 7–14 days (n = 55, 67·9%), SFG presented with fever of shorter duration of <7 days (n = 33, 64·7%), and typhus fever group presented with fever of longer duration of >14 days (n = 20, 50%).

Scrub typhus patients had prominent myalgia (n = 66, 81·5%) and headache (n = 59, 72·8%) associated with fever. The patients of the SFG had gastrointestinal complaints such as vomiting (n = 38, 74·5%) and diarrhea (n = 7, 13·7%). Cough (n = 26, 65%) and abdominal pain (n = 17, 42·5%) were common in the typhus group. Apart from the classical symptoms, few patients in scrub typhus group presented with atypical symptoms of altered sensorium (n = 5, 6·2%) and seizures (n = 2, 3·9%). [Table 1] elucidates the symptoms that the patients presented with.
Table 1: Symptoms seen in the various rickettsial groups

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Macular rash was seen in 56·9% patients of the SFG. Eschar (8·6%, n = 7) and splenomegaly (51·9%, n = 42) were among scrub typhus patients. Hepatomegaly (35%, n = 14) predominated the clinical picture in the typhus fever groups, whereas a few patients also showed lymphadenopathy. [Table 2] details the physical signs seen in these patients.
Table 2: Signs seen in the various rickettsial groups

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The laboratory findings are shown in [Table 3]. Leucopenia and thrombocytopenia were common in all the groups of patients. Other laboratory abnormalities such as transaminitis, altered renal function test, increase in total bilirubin, and hypoalbuminemia were seen in a significant number of patients among scrub typhus group.
Table 3: Laboratory features in the various rickettsial groups

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Complications, including nonoliguric renal failure, pleural effusion, meningoencephalitis, liver cell failure, and acute respiratory distress syndrome (ARDS), were observed among the patients of scrub typhus group. Most common complication overall was pleural effusion (13·5%) followed by nonoliguric renal failure (6%). Scrub typhus contributed to the bulk of these complications (83·3% and 87·5% of the total burden, respectively). Details of the complications in each group are highlighted in [Table 4].
Table 4: Complications in the various rickettsial groups

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All patients were treated with oral doxycycline along with symptomatic treatment. Response to doxycycline was seen within 36–48 h in most of our cases. Where there was no response to doxycycline, azithromycin 500 mg per oral for 5 days was added and fever subsided. There was one mortality during the study due to ARDS in scrub typhus group.


  Discussion Top


Rickettsial infections are a major contributor to the burden of acute febrile illness in India. It is challenging to diagnose these infections and differentiate them from other infections such as dengue and malaria in the early stages. The clinical manifestations of most rickettsioses represent a continuous spectrum. In the absence of definite pathognomonic signs, there are clues-signs and symptoms highly suggestive of the etiology. However, not all cases present with the set of typical clinical manifestations that aids in prompt recognition. In resource-poor countries, most cases are diagnosed based on the clinical suspicion together with a positive serology. As such, the clinical acumen and awareness of the treating physician have a great role in the diagnosis and management of these cases. This study aimed to present a clinical profile that may help to identify rickettsial infections in our patients. Using Weil-Felix and a syndromic approach, we further analyzed the differences between the rickettsioses prevalent in this part of the world.

Rickettsial infections generally begin as an acute, nonspecific, febrile illness often accompanied by headache, myalgia, nausea, and vomiting. After 3–5 days of illness, a macular, maculopapular, or even a vesicular rash appears.[10] An eschar at the site of an ectoparasite bite, with local or generalized lymphadenopathy may also occur.[10]

Three syndromic presentations are seen. (a) Rickettsioses may present as exanthematous fever with a centrifugal rash distribution and a low probability of inoculation eschar (e.g., Rickettsia typhi ), (b) organisms can present with an inoculation eschar and a maculopapular/purpuric rash (e.g., Rickettsia felis , Rickettsia conorii subsp. Indica, Orientia tsutsugamushi ). (c) Finally, there may be a probability of inoculation eschar and a vesicular rash (Rickettsia akari ).[4]

The eschar may be the only clinical sign that differentiates scrub typhus and tick-borne SFG Rickettsia from other infectious diseases, including murine typhus.[11] Travelers with imported rickettsial diseases often become sick before or within a few days of returning from a disease endemic region. Because the incubation period for most rickettsial infections is 6–20 days, an illness that begins more than 18 days after the return from a disease-endemic area is unlikely to be rickettsial in origin.[2]

Most of our patients had nonspecific symptoms and signs mimicking any acute febrile illness. However, the features suggestive of rickettsioses such as the presence of rash or eschar, age, occupation, and an average febrile period of 7–10 days lend to clinically suspect these cases.

In the present study, the mean age group was 39.2 years with a slight majority of males. Scrub typhus was the most common rickettsiosis found in our study (47·1%), typhus group constituted 23.3% and SFG 29·7%. The study conducted by the National Centre for Disease Control, Delhi, which did serosurvey for rickettsial fever in two phases from 1999 to 2004 and 2005–2009 found scrub typhus (48·2%) to be most common, followed by SFG (27·5%) and typhus group (6·8%).[3]

Scrub typhus infection showed definite seasonal variation in this study. Seventy-three cases (90·1%) occurred during the period from June to October which is consistent with a study by Mathai et al .[12] and Hamaguchi et al .[11]

The clinical illness may vary from mild febrile illness to severe fatal disease. Scrub typhus patients present with fever (100%) of duration 7–14 days (67·9%), followed by myalgia (81·5%) and headache (72·8%). Few patients presented with atypical symptoms such as altered sensorium (6·2%) and seizures (2·5%). These findings are similar to a study done by Mitra et al .,[13] where fever followed by headache were the predominant symptoms. The most common clinical sign was splenomegaly (51·9%), which was consistent with a study done by Gurung et al .[14]

In scrub typhus, usually, an eschar of approximately 5–20 mm in diameter is formed at the site bitten by trombiculid mites. This may be considered pathognomonic for the diagnosis of scrub typhus. However, only 7 (8·6%) of our patients presented with eschar. In a study done by Takhar et al ., there was a similar paucity of eschar seen in patients of scrub typhus. Only 8·4% had the typical feature.[15]

Spotted fever group presented with fever of shorter duration of <7 days (64·7%), and gastrointestinal symptoms such as vomiting (74·5%) and diarrhea (13·7%) were predominantly seen. SFG had macular rash as predominant sign. It was seen in 56·9% of the patients. These findings were similar to the study done by Gupta et al .[16]

Typhus group presented with fever of longer duration of more than 14 days (50%) and respiratory symptoms such as cough (65%). Hepatomegaly was present in 35% and lymphadenopathy in 7·5%. These findings are consistent with a study done by Hamaguchi et al . where hepatomegaly was seen in 39% and lymphadenopathy seen in 19·7% of patients.[11]

Leucopenia and thrombocytopenia were common laboratory feature seen in scrub typhus group of patients. Other laboratory abnormalities such as transaminitis, altered renal function, increase in total bilirubin, and hypoalbuminemia were seen in a significant number of patients among scrub typhus group.

The patients with hypoalbuminemia (n = 73) had a greater predilection to complications (n = 41, 56·1%). This is in keeping with the findings of a previous study undertaken by Kamath el.al.[17]

Complications, including nonoliguric renal failure, pleural effusion, meningoencephalitis, liver cell failure, and ARDS, were observed among the patients of scrub typhus group. In this set of patients, the most common complication was pleural effusion (24·7%) followed by nonoliguric renal failure (12·3%). Studies done by Gupta et al .,[16] Mathai et al .,[12] and Takhar et al .[15] showed similar finding with the most common complication being acute renal failure and ARDS.

The statistically significant differences between the rickettsial groups in terms of syndromic presentation were evaluated and obtained using the ANOVA. The results are as follows: (a) scrub typhus: Was more likely to present with fever 7–14 days (P = 0.03); splenomegaly (P = 0.023) and eschar (P = 0.014) were significant examination findings; in the laboratory, it presents with increased serum glutamic oxaloacetic transaminase/serum glutamic-pyruvic transaminase (P = 0.024) and decreased albumin (P = 0.021). (b) SFG had a preponderance toward fever <7 days (P = 0.043), vomiting (P = 0.03), and joint pain (P = 0.049). Macular rash (P = 0.04) was observed clinically. Pleural effusion (P = 0.021) was a significant complication. (c) Typhus group had fever >14 days (P = 0.04), associated with cough (P = 0.019), and abdominal pain (P = 0.039). Hepatomegaly (P = 0.045) was a significant clinical findings.

All patients were treated with oral doxycycline along with symptomatic treatment. Response to doxycycline was seen within 36–48 h in most of our cases except in three cases. In these cases, azithromycin 500 mg per oral for 5 days was added. With the administration of this regimen, the fever subsided. There was one mortality during the study due to ARDS in scrub typhus group (mortality rate of 1·2%). Takhar et al . have also reported mortality due to scrub typhus in their study although in higher numbers.[15]

Limitations of the study

Weil-Felix lacks sensitivity. However, it is readily available and provides a rapid diagnostic option for rickettsial infections when interpreted in the correct clinical context. As confirmation of the diagnosis is difficult during the acute phase, and proper treatment is essential for the rapid recovery and prevention of complications, presumptive therapy with anti-rickettsial drugs was started whenever a case of rickettsiosis was suspected.

Therefore, the fourfold rise in titers which aids in the retrospective diagnosis of Rickettsia using Weil-Felix was not done. Less than 10% of the cases were subjected to further IgM ELISA assays for confirmation. Therefore, the above cases strictly meet only the definition of “probable rickettsial fever” as per the Department of Health Research-Indian Council of Medical Research Guidelines for the Diagnosis and Management of Rickettsial Diseases in India.[18]

Rickettsial infections are a major cause of acute febrile illnesses among the residents of Southeast Asia and remain an important differential diagnosis for febrile returned travelers from that region. However, many challenges remain in the diagnosis and management of rickettsial infections. From an individual physician's perspective, rickettsial infections remain a diagnostic challenge in resource-poor settings. Therefore, it is important to recognize the clinical features promptly, include rickettsioses in the differential diagnoses, and consider early initiation of appropriate treatment.


  Conclusion Top


Rickettsial infections are a major cause of acute febrile illnesses among the residents of Southeast Asia and remain an important differential diagnosis for febrile returned travelers from that region. However, many challenges remain in the diagnosis and management of rickettsial infections. From an individual physician's perspective, rickettsial infections remain a diagnostic challenge in resource-poor settings. Therefore, it is important to recognize the clinical features promptly, include rickettsioses in the differential diagnoses, and consider early initiation of appropriate treatment

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Kamath V, Ganguly S, Bhatia JK. Rickettsial infections: Spreading beyond boundaries. In: Narsimalu G, editor. Progress in Medicine. Vol. 29. Mumbai: Jaypee; 2019. p. 195-9.  Back to cited text no. 1
    
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Acestor N, Cooksey R, Newton PN, Ménard D, Guerin PJ, Nakagawa J, et al . Mapping the aetiology of non-malarial febrile illness in Southeast Asia through a systematic review-terra incognita impairing treatment policies. PLoS One 2012;7:e44269.  Back to cited text no. 2
    
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Mittal V, Gupta N, Bhattacharya D, Kumar K, Ichhpujani RL, Singh S, et al . Serological evidence of rickettsial infections in Delhi. Indian J Med Res 2012;135:538-41.  Back to cited text no. 3
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Kangra T, Pradesh H, Rani S, Thakur K, Sood A, Chauhan V, et al . Comparison of Weil Felix Test and IgM ELISA in the diagnosis of Scrub. Int J Heal Sci Res 2016;6:28-32.  Back to cited text no. 5
    
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Kularatne SA, Gawarammana IB. Validity of the Weil-Felix test in the diagnosis of acute rickettsial infections in Sri Lanka. Trans R Soc Trop Med Hyg 2009;103:423-4.  Back to cited text no. 6
    
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Hamaguchi S, Cuong NC, Tra DT, Doan YH, Shimizu K, Tuan NQ, et al . Clinical and epidemiological characteristics of scrub typhus and murine typhus among hospitalized patients with acute undifferentiated fever in Northern Vietnam. Am J Trop Med Hyg 2015;92:972-8.  Back to cited text no. 11
    
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Mathai E, Rolain J, Verghese G, Abraham O, Mathai D, Mathai M, et al . Outbreak of scrub typhus in Southern India during the Cooler Months. Ann N Y Acad Sci 2003;990:359-64.  Back to cited text no. 12
    
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Mitra S, Gautam I, Jambugulam M, Abhilash KP, Jayaseeelan V. Clinical score to differentiate scrub typhus and dengue: A tool to differentiate scrub typhus and dengue. Glob Infect Dis 2017;9:12-7.  Back to cited text no. 13
    
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Gurung S, Pradhan J, Bhutia P. Outbreak of scrub typhus in the North East Himalayan region-Sikkim: An emerging threat. Indian J Med Microbiol 2013;31:72.  Back to cited text no. 14
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[PUBMED]  [Full text]  


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